Twickenham was carefully planned. The streets were built from the northeast to southwest direction based on the Big Spring (see images below). However, due to anti-English feeling during the War of 1812, the town name was changed to Huntsville to honour John Hunt, who had been forced to move to other land south of the new city.

In 1811, Huntsville became the first official town in Alabama. However, the recognized "birth" year of the city is 1805. This was the year of John Hunt's arrival. The city's sesquicentennialanniversary was held in 1955 and the bicentennial was celebrated in 2005.

Huntsville firstly opposed secession from the Union in 1861, but provided many men for the state's defense. The 4th Alabama Infantry Regiment, led by Col. Egbert J. Jones of Huntsville, fought at the Battle of Manassas. It was the first major battle of the American Civil War. The Fourth Alabama Infantry, which contained two Huntsville companies, were the first Alabama troops to fight in the war. Eight generals of the war were born in or near Huntsville.

After the Civil War, Huntsville became a center for cotton textile mills, such as Lincoln, Dallas and Merrimack. Each mill had its own housing community. It included everything the mill workers needed (schools, churches, grocery stores, theatres, and hardware stores, all within walking distance of the mill).

During the 1930s, industry decreased in Huntsville because of the Great Depression. Huntsville became known as the Watercress Capital of the World[6] because of its harvest in the area. Madison County produced most cotton in Alabama during this time.[6]

By 1940, Huntsville was still a small quiet town with a population of only 13,150 inhabitants. This quickly changed with the beginning of World War II. Huntsville was chosen as the location of Huntsville Arsenal, with chemical and munitions manufacturing plants.[7] The Arsenal was almost closed in 1949 when it was no longer needed,[8] but it saw new life when Major GeneralHolger Toftoy with support from Senator John Sparkman convinced the U.S. Army to choose Huntsville as the location for its missile research program. In 1950, General Toftoy brought German rocket scientist Wernher von Braun and his team to Redstone Arsenal to develop what would eventually become the United States' space program.[9]

Huntsville's economy was nearly crippled and growth came to a near standstill in the 1970s following the closure of the Apollo program. The emergence of the Space Shuttle and the ever-expanding field of missile defense in the 1980s helped give Huntsville a resurgence that has continued into the 21st century.